Title

Author

Degree Type

Dissertation

Date of Award

2014

Degree Name

Doctor of Philosophy

Department

Animal Science

Major

Nutritional Sciences

First Advisor

Lance H. Baumgard

Abstract

Heat stress (HS) is a major environmental hazard for human health and animal agriculture. Changes in metabolism and specifically altered insulin action appear to be critical for the adaptation and ultimately survival to a severe heat load. However, our knowledge of the physiological and metabolic consequences of HS is woefully insufficient. Understanding the biology of HS is critical in order to develop treatment protocols and mitigation strategies against its deleterious effects on both humans and livestock. Interestingly, HS elicits a metabolic profile that somewhat resembles models of endotoxemia/sepsis. Moreover, HS negatively affects intestinal health and the subsequent increase in the permeability to luminal pro-inflammatory molecules might be the link between both models. Therefore, alleviating the effects of HS on the intestinal barrier function may have the potential to prevent or ameliorate its impact on animal health and productivity.

Studies conducted for this dissertation utilized sus scrofa as the model, due to the pig's relevance in both animal agriculture and the biomedical field. Study 1 (chapter 2) was conducted to determine the temporal effects of HS on basal and stimulated metabolism. Results indicated that HS decreases both basal and adrenergic-induced adipose tissue mobilization. Heat stress increased basal insulin secretion and decreased circulating thyroid hormones. Early heat exposure decreased glucose disposal in response to a glucose tolerance test, which might suggest increased whole body insulin resistance. However when considering the glucose and insulin responses together, HS pigs required less insulin compared to controls in order to dispose of a similar amount of glucose, which would actually indicate increased insulin sensitivity.

Based on the conflicting results obtained in study 1 regarding insulin action, in study 2 (chapter 3) we aimed to define the effects of HS on whole-body insulin action. For this purpose we performed a hyperinsulinemic euglycemic clamp and concluded that, relative to controls, HS pigs required a greater rate of glucose infusion to maintain euglycemia. Further, molecular markers of insulin signaling prior and after insulin stimulation, suggested that the skeletal muscle is partially responsible for the increase in insulin-stimulated glucose uptake observed during HS.

Heat stress has deleterious effects on intestinal health that may ultimately mediate its effects on energetic metabolism and productivity. Studies 3 and 4 (chapters 4 and 5) objectives were to establish the feasibility of dietary interventions in order to mitigate HS-induced intestinal barrier dysfunction. Previous research had demonstrated that dietary zinc and whey protein improve intestinal health in a variety of bowel disease models, which led us to hypothesize that their supplementation would alleviate the negative effects of HS on intestinal permeability. Results from these studies indicated that supplemental zinc improves aspects of small intestinal integrity during severe HS. In contrast, the tested dairy products did not mitigate the deleterious consequences HS has on intestinal barrier function.

In conclusion, studies 1 and 2 demonstrated that HS markedly alters both lipid and carbohydrate metabolism. Specifically, HS decreases adipose tissue mobilization and increases whole-body insulin sensitivity. In addition, studies 3 and 4 proved that dietary interventions aimed to improve intestinal integrity during HS are plausible. A better understanding of the relative contribution of the intestinal barrier dysfunction to the heat-induced effects on metabolism and ultimately on nutrient partitioning is a prerequisite for designing targeted strategies to mitigate the consequences of HS on human health and animal productivity.